Publication: Implication of hepsin from primary tumor in the prognosis of colorectal cancer patients
Authors
Zaragoza-Huesca, David ; Nieto-Olivares, Andrés ; García-Molina, Francisco ; Ricote, Guillermo ; Montenegro, Sofía ; Sánchez-Cánovas, Manuel ; Garrido-Rodríguez, Pedro ; Peñas-Martínez, Julia ; Vicente, Vicente ; Martínez Díaz, Francisco ; Lozano, María Luisa ; Carmona-Bayona, Alberto ; Martínez-Martínez, Irene
item.page.secondaryauthor
item.page.director
Publisher
MDPI
publication.page.editor
publication.page.department
DOI
https://doi.org/10.3390/ cancers14133106
item.page.type
info:eu-repo/semantics/article
Description
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/. This document is the Published version of a Published Work that appeared in final form in Cancers. To access the final edited and published work see https://doi.org/10.3390/
cancers14133106
Abstract
Hepsin is a type II transmembrane serine protease whose deregulation promotes tumor invasion by proteolysis of the pericellular components. In colorectal cancer, the implication of hepsin is unknown. Consequently, we aimed to study the correlations between hepsin expression and different clinical-histopathological variables in 169 patients with localized colorectal cancer and 118 with metastases. Tissue microarrays were produced from samples at diagnosis of primary tumors and stained with an anti-hepsin antibody. Hepsin expression was correlated with clinical histopathological variables by using the chi-square and Kruskal–Wallis tests, Kaplan–Meier and Aalen–Johansen estimators, and Cox and Fine and Gray multivariate models. In localized cancer patients, high-intensity hepsin staining was associated with reduced 5-year disease-free survival (p-value = 0.16). Medium and high intensity of hepsin expression versus low expression was asso ciated with an increased risk of metastatic relapse (hazard ratio 2.83, p-value = 0.035 and hazard ratio 3.30, p-value = 0.012, respectively), being a better prognostic factor than classic histological variables. Additionally, in patients with localized tumor, 5-year thrombosis cumulative incidence
increased with the increment of hepsin expression (p-value = 0.038). Medium and high intensities of hepsin with respect to low intensity were associated with an increase in thrombotic risk (hazard ratio 7.71, p-value = 0.043 and hazard ratio 9.02, p-value = 0.028, respectively). This relationship was independent of previous tumor relapse (p-value = 0.036). Among metastatic patients, low hepsin expression was associated with a low degree of tumor differentiation (p-value < 0.001) and with major
metastatic dissemination (p-value = 0.023). Hepsin is a potential thrombotic and metastatic biomarker in patients with localized colorectal cancer. In metastatic patients, hepsin behaves in a paradoxical waywith respect to differentiation and invasion processes.
publication.page.subject
Citation
Cancers 2022, 14, 3106
item.page.embargo
Collections
Ir a Estadísticas
Este ítem está sujeto a una licencia Creative Commons. http://creativecommons.org/licenses/by/4.0/